PROJECT SUMMARY Kinases regulate normal physiological response to environmental perturbations. When dysregulated, either through aberrant expression or mutation, protein and lipid kinases have been implicated in a host of diseases, from metabolic disorders to cancer. Accordingly, many of the targeted therapeutics for cancer have been generated against oncogenic kinases. Unfortunately, the therapeutic efficacy of these agents has been largely disappointing due to the emergence of resistance caused in part by rewiring of the signaling network or resistance mutations. Understanding the normal physiological role of protein kinases, their catalytic activation mechanisms, as well as their altered substrates and signaling networks in disease states, will significantly improve our ability to selectively target disease-associated kinases and will enable the development of next- generation targeted combinatorial therapeutics with greatly increased efficacy. There are three specific objectives of the FASEB 2016 Kinase Signaling Network Regulation Conference. The first objective is to describe the state of the art in kinase signaling network regulation: structure, function, localization, regulation, interactions, and targeting in both normal and pathological cell states. To accomplish this goal we have planned a series of keynote and plenary speakers from many of the leading experts in the field, multiple short talks selected from the poster abstracts, poster sessions, several focused workshops, and informal discussions. Since the challenges in this field are daunting and will require collaborative efforts to solve them, the second goal is to enhance interactions between different biological fields: academia, industry, and clinical science. To enhance cross-cutting information transfer between fields, we have invited a diverse set of speakers representing different diseases, fundamental research, and translational applications, from different employment sectors. The third objective is to invest intellectually and financially in the future by supporting promising young trainees. The goal is to encourage trainees to be successful and stay in the field by providing intellectual support through discussions with senior scientists, poster sessions, opportunities to speak, awards that recognize their achievements, and by providing financial support with competitive travel awards. The expected outcomes are increased collaborations, retention of young scientists in the field, identification of new developmental processes and diseases linked to kinase signaling, and exploration of new approaches for identifying and developing novel therapeutic targets.